Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Automated scans let scientists track drugs’ broad effects on cells

12.11.2004


’Cytological profiling’ could streamline early phases of drug discovery

Bringing an unprecedented level of automation to microscopy, scientists at Harvard University have developed a powerful new method of visualizing drugs’ multifaceted impact on cells. The technique, which could eventually become a standard tool for drug discovery, is described this week in the journal Science.

Steven J. Altschuler and Lani F. Wu, mathematicians skilled in developing models to find meaningful patterns among mountains of data, worked with Timothy J. Mitchison of Harvard Medical School to automate microscopic imaging of drug-treated cells and recast the resulting scans in a computer-friendly format. The result: a method dubbed "cytological profiling" that trains computers to recognize cell status and health from cellular images, virtually automating microscopic scanning for various types of abnormalities.



"The resulting profiles of cellular changes wrought by drugs at various dosages provide information on drug mechanism that is highly relevant to understanding the specificity and toxicity of drugs," says Altschuler, research fellow at the Bauer Center for Genomics Research in Harvard’s Faculty of Arts and Sciences. "The information gleaned includes many key indicators of drugs’ potential usefulness and limitations as medicines."

"We actually started out on this project thinking that this could be a good research tool," adds Wu, research fellow at the Bauer Center. "We’ve now discovered, to our surprise, that it may also prove a powerful tool for drug discovery."

High-throughput cytological profiling lets scientists test numerous variables at once, wringing countless discrete cellular measurements from a single experiment. Faced with scores of drugs holding the potential to combat a given disease, researchers could hone in on the most promising drugs in a fraction of the time of current methods.

"This technique employs ’guilt by association’ -- if two drugs’ cytological profiles look similar, they probably work through similar mechanisms," Altschuler says. "It’s particularly useful for understanding drug action because it allows us to look at many concentrations of a drug, which is essential for comparing two drugs that may have different potency but act on the same target."

Since they are hardy and flourish even outside the body, the Harvard team used human cancer cells. They placed the cells in 384 minuscule wells in a plastic dish, injected each well with one of 100 drugs -- both medicines and toxins -- at different concentrations, and finished off the plates with11 chemical probes for different proteins and DNA.

After 20 hours of cell growth, the researchers used automated microscopy to collect some half a million images of the treated cells, followed by approximately 5 billion individual measurements of the size, shape, and quantity of different proteins, DNA, and organelles in each. Software developed by Altschuler, Wu, and colleagues allowed them to convert this copious data into profiles of the effects of each drug, yielding distinctive red-and-green "fingerprints" for each, not unlike the color-coded data from a DNA chip.

However, unlike DNA chips that meld bountiful data into an "average" denoted by dots of color on a grid, cytological profiling preserves individual data points -- so researchers can go back and analyze fine-grain information.

"By allowing quantitative measurement of many proteins and structures in cells over many samples, and systematic comparison between samples, our method brings microscopy into the ’-omics’ era, like genomics and proteomics," says Mitchison, of Harvard Medical School’s Institute of Chemistry and Cell Biology and Department of Systems Biology. "This really allows us a much broader view of how cells are affected by a wide range of perturbations."

Cytological profiling may be especially useful, Mitchison says, for evaluating drug candidatesin areas where making a drug with a highly specific biochemical effect is difficult, such as kinase inhibitors. Future applications may include testing the response of cancer cells with different genetic profiles to a spectrum of anti-cancer drugs, which could help predict clinical responses in individual patients.
Alschuler, Wu, and Mitchison were joined in this research, sponsored by the National Cancer Institute and Howard Hughes Medical Institute, by co-authors Zachary E. Perlman and Yan Feng at Harvard Medical School and Michael D. Slack in the Bauer Center for Genomics Research.

Steve Bradt | EurekAlert!
Further information:
http://www.harvard.edu

More articles from Life Sciences:

nachricht Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care

nachricht Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>